A wound is defined as a break in the continuity of the skin. It can be caused by traumatic injury such as burn, cut or scrape. A prompt treatment will avoid complications such as infection and inflammation. The usual and conservative methods of closing a wound are application of various medicaments or alternatively, the wound is closed by surgical procedures of suturing the wounds edges, by grafting cultured skin or by split skin grafts. The aim of all of the above is to promote the growth of granulation tissue that may or may not follow promptly, depending on adequate blood supply bringing into the wound the nutrients that the cells need for growth.
The concept of this method is to use a proactive rather then protective treatment. That is, following the usage of antiseptic or anti-inflammatory medicaments, that when indicated are the standard treatments, the treatment then should be followed by induction of a stimulatory treatment.
The idea is to create microenvironment favorable for wound healing after assuring that the wound is clinically clean. This method aims to stimulate and support growth of connective tissue components originating from the wound bed and its peripheral walls. The granulation tissue filling the wound space will create the substratum required for re-epithelialization and wound closure.
When injury to the skin occurs, a set of complex biochemical events takes place in a cascade leading to repair the damage.
Wound healing, or wound repair, is an intricate process in which the skin (or another organ-tissue) repairs itself after injury. In normal skin, the epidermis (outermost layer) and dermis (inner or deeper layer) exists in steady-state equilibrium, forming a protective barrier against the external environment. Once the protective barrier is broken, the normal (physiologic) process of wound healing is immediately set in motion.
The classic model of wound healing is divided into three or four sequential, yet overlapping, phases: (1) homeostatic, (2) inflammatory, (3) proliferative and (4) remodeling.
1. Homeostasis occurs shortly after the injury; platelets (thrombocytes) migrate to the injury site to form a fibrin clot. This clot acts to control active bleeding.
2. During the inflammatory phase, bacteria and debris are removed by phagocytosis and the simultaneous release of growth factors causes migration and division of the cells that take part in the proliferative phase.
3. The proliferative phase of wound healing is characterized by angiogenesis, collagen formation and deposition, growth of granulation tissue, epithelialization, and wound contraction. Angiogenesis involves formation of new blood vessels by the vascular endothelial cells. During the fibroplasia and the granulation tissue formation, the fibroblasts grow and form a new, provisional extra cellular matrix by excreting collagen and fibronectin. Concurrently, re-epithelialization of the epidermis occurs, where epithelial cells proliferate and migrate over the granulation tissue, providing cover for the new tissue.
4. Remodeling phase comprises the contraction process where the wound becomes smaller due to contraction of myofibroblasts that grip the wound edges and contract. In the maturation and remodeling phase, collagen is remodeled and realigned along tension lines and cells that are no longer needed are removed by apoptosis.
However, the healing is process that is not only complex but also fragile, and susceptible to interruption or failure leading to the formation of chronic non-healing wounds. Factors which may contribute to this include diabetes, topical or systemic venous and/or arterial insufficiencies, old age, and infection.
Thus, a wound is defined as a break in the continuity of the skin. It can be caused by traumatic injury such as burn, cut or scrape. A prompt treatment will avoid complications such as infection and inflammation. The usual and conservative methods of closing a wound are application of various medicaments or alternatively, the wound is closed by surgical procedures of suturing the wounds edges, by grafting cultured skin or by split skin grafts. The aim of all of the above is to promote the growth of granulation tissue that may or may not follow promptly, depending primarily on adequate blood supply that brings into the wound the nutrients that the cells need for growth.
The concept of this method is to use a proactive rather then protective treatment. That is, following the usage of antiseptic or anti-inflammatory medicaments, that when indicated are the standard treatments, the treatment then should be followed by induction of a stimulatory treatment.
The idea is to create a microenvironment favorable for wound healing after assuring that the wound is clinically clean. The wound and its surrounding area will be moisturized, exposed to the rich nutrients, protected from dehydration by the gelling of the media and dressed with sterile gauze which allows the oxygen in the air to penetrate the dressing and reach the wound surface. This method aims to stimulate and support growth of connective tissue components originating from the wound bed and its peripheral walls. The proliferating granulation tissue filling the wound space will create the substratum required for re-epithelialization leading to wound closure.
This invention is based on human tissue and cell culture technology of growing fibroblast and epithelial cells in culture. Utilizing similar nutrient media supplements with insulin or alternatively with substances possessing insulin-mimetic features, the milieu in the wound becomes moist and enriched with the nutrients. These are the requirements for cells proliferation and the growth of the granulation tissue including new capillaries into the wound space.
Wound healing involving surgical procedures are successful only when the application of the graft is performed onto viable granulation tissue. Success of the graft take is dependent on the proliferation of granulation tissue that can be achieved only when adequate microenvironment is created in the wound. Thus the viability of the grafted tissue over the wound is the limiting by the availability of the materials for obtaining success of the take and the healing process.
There are multiple causes of injuries, damage by exposure to excessive hot or cold temperatures, mechanical damage by scraps, stabs or cuts, chemical damage due acid or alkaline burns or damage by radiation. All of these wounds heal by proliferation of granulation tissue that fills the space within the wound and is followed by growth of epithelial cells that invade the wound space from the bed and the periphery of the wound forming the new granulation tissue and culminating in complete wound closure. However, if the wound is infected or if the blood supply is insufficient for tissue growth, the healing process fails. In the first case application of antiseptics can overcome the contamination and eventually the wound will close, but in the second case of insufficient blood supply the wound becomes chronic. Serum-free cell culture media supplemented with insulin or substances with insulin-like activity (e.g. MHCP or MHCP and insulin-like growth factor, preferably human), preferably a mixture of insulin and a substance with insulin-like activity will supply the cells in the wound with the nutrients required for the process of wound healing.
From antiquity till today the beneficial effects of cinnamon were recognized. It was used as an ingredient of the sacred oil (Exodus 30:23) and as a spice (Proverbs 7:17, Song of Solomon 4:14 and Revelation 18:13). Furthermore, the essential oil of cinnamon extracted from the cinnamon bark was traditionally used as anti bacterial, anti microbial, anti infectious, anti viral and anti fungal agent. It was also used to increase blood flow in areas where the circulation was restricted. Majno G. in his book The Healing Hand, describes ancient methods of treating wounds including the used of honey as a powerful bacteriostatic agent and the use of cinnamon for its beneficial properties on wound healing.
Berrio L. F et al., report that cinnamon and Brewer's yeast potentates the activity of insulin. In two publications, in Jarvill-Taylor J. Anderson R. A. et. al., and in Karlee J. Jarville-Taylor et. al. demonstrated the insulin-like activity was found in substances including cinnamon. They report that, in adipocytes cell cultures, Methyl Hydroxy Chalcone Polymer-(MHCP), extracted from cinnamon, acts as a mimetic of insulin. This component that is found in cinnamon affects glucose metabolism and the conversion of glucose to energy that then is utilized to enhance the cells multiplication process. In addition it renders insulin much more efficient and thus acts synergistically with insulin. In addition, Kamath J. V et. al., report the hydroxyproline increase in the granulation tissue content of the wound due to treatment with cinnamum zeylanicum. Anderson R, et. al recently describes the effectiveness of polyphenol type-A polymer extracted from cinnamon as a powerful insulin mimetic substance.
Karalee J. T. and Stapleton S. R. reported the usage of cinnamon extract to boost insulin sensitivity and that Selenium was implicated in potentiating the insulin-like activity since it stimulates glucose uptake and regulates glycolysis, gluconeogenesis and fatty acids synthesis. Alt S. et al., describes using insulin and other agents to work in synergy to accelerate the healing process. However neither of them used serum-free cell culture media such as MEM, DMEM, BGJ or MCDB as a substrate.
Insulin has been implicates in triggering the cascade of the wound healing process. C. Linge claims that when insulin is injected into the wound area it enhances re-epithelialization of the wound. It is well known that sugar has been successfully used in treating wounds during the First World War, and honey has been used since antiquity to treat wounds both with definite success. Nakao H. et. al. reports that the mixture of sugar and povidone-iodine stimulated wound healing by stimulating the keratinocytes and fibroblasts activity.
In a series of clinical trials Lindenbaum E. S. et al., used a formulation containing serum-free cell culture nutrient medium MCDB 153 to successfully treat atrophic recalcitrant wounds. Lindenbaum E. S et al. also reported the successful use of serum-free cell culture media MCDB 153 supplemented with insulin to treat recalcitrant chronic wounds.